This component of the proposed SPIRCAP describes two specific aims: 1. To screen clinically available agents that interfere with the acute neurochemical and behavioral responses to cocaine in behavioral, microdialysis and self-administration paradigms. Promising functional cocaine antagonists identified would subsequently be evaluated in human laboratory studies. 2. To screen clinically available pharmacotherapies that interfere with the sensitized response to repeated cocaine administration. In abstinent patients, such pharmacotherapies may protect against relapse to dependence by preventing a single episode of cocaine abuse from producing and especially intense subjective response.